Dysregulated transcriptional programs sustain proliferation, survival, and resistance to therapy in tumor cells. The lab investigates how cancer cells take control of the RNA polymerase II (RNAPII) core machinery and disrupt accuracy, timing, and organization of gene expression.

Under physiological conditions, transcription of coding and noncoding genes is subjected to multiple checkpoints and quality control mechanisms, from start to finish. Conversely, dysregulated RNAPII activity leads to genome-wide buildup of R-loops, hypertranscription of transposable elements (such as Alu and ERVs), defective splicing of mRNAs and readthrough of genes after the polyA site (DOGs). Taken together, global malfunction of RNAPII results in chronic activation of stress response pathways and increased DNA damage, thereby paving the way to unchecked growth.

A central focus of the lab is investigating the role of the Integrator-PP2A complex as a guardian of transcriptional integrity. Integrator is an RNA-endonuclease that controls polymerase activity from the promoter-proximal pausing through productive elongation, all the way until transcripts are released from the fork and RNAPII is terminated. Our lab has discovered how the PP2A phosphatase associates with Integrator to modulate kinase-dependent checkpoints. Now, to further investigate how phosphatase and RNA endonuclease activities cooperate to surveil global transcription, we use nascent-RNA profiling, proteomics, structural modeling, and genetic perturbation approaches in models of leukemia and ovarian cancer.

Myeloid cells are exceptionally adaptable: common progenitors generate monocytes, macrophages, neutrophils, dendritic cells, and myeloid-derived suppressor cells through dynamic changes in enhancer activity, chromatin organization, and gene expression. The Lab studies how these epigenetic programs establish normal myeloid identity and how they are repurposed during inflammation, cancer, and immunosuppression.

Our earlier work defined developmental enhancer programs that drive myeloid differentiation and identified EGR1 as a key regulator of inflammatory enhancers in human macrophages. We now extend these studies to determine how transcription factors, enhancer networks, and three-dimensional genome architecture support the functional diversity of myeloid cells across developmental and inflammatory contexts.

A current focus is the role of nuclear organization in myeloid-cell plasticity. We are investigating how compartmentalization at the nuclear lamina shapes enhancer engagement and regulates tissue-specific transcriptional programs as monocytes differentiate into macrophages or adopt specialized immune states. By combining high-resolution microscopy, DNA and RNA FISH, chromatin profiling, nascent-RNA sequencing, and three-dimensional genome analyses, we aim to connect nuclear position to gene-regulatory function.

We also study how tumors reshape the myeloid compartment. In tumor-bearing hosts and patient samples, we investigate whether long-lasting epigenetic changes in myeloid progenitors establish suppressive programs that give rise to tumor-associated macrophages and myeloid-derived suppressor cells. Defining these regulatory states may identify biomarkers of immunotherapy response and reveal strategies to reprogram immunosuppressive myeloid cells in cancer.